ArticlePloS one2015
Visualization of Active Glucocerebrosidase in Rodent Brain with High Spatial Resolution following In Situ Labeling with Fluorescent Activity Based Probes.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Isomer-Resolved Mass Spectrometry Imaging Reveals Regional and Age-Dependent Glycolipid Metabolism in Rat Brain.ACS central science · 2026Article
- Spatially Resolved Mapping of Monoacylglycerol Lipase Activity in the Brain.ACS chemical neuroscience · 2025Article
- Synaptic vesicle endocytosis deficits underlie cognitive dysfunction in mouse models of GBA-linked Parkinson's disease and dementia with Lewy bodies.Nature communications · 2025Article
- Chiral Fluorescent Antifungal Azole Probes Detect Resistance, Uptake Dynamics, and Subcellular Distribution inJACS Au · 2024Article
- Chemical Probes to Control and Visualize Lipid Metabolism in the Brain.Accounts of chemical research · 2022Review
- Neuronal activity induces glucosylceramide that is secreted via exosomes for lysosomal degradation in glia.Science advances · 2022Article
- Lipid Dyshomeostasis and Inherited Cerebellar Ataxia.Molecular neurobiology · 2022Review
- Chemically diverse activity-based probes with unexpected inhibitory mechanisms targeting trypsin-like serine proteases.Frontiers in chemistry · 2022Article
- Evaluation of Strategies for Measuring Lysosomal Glucocerebrosidase Activity.Movement disorders : official journal of the Movement Disorder Society · 2021Review
- Xylose-Configured Cyclophellitols as Selective Inhibitors for Glucocerebrosidase.Chembiochem : a European journal of chemical biology · 2021Article
- Decreased glucocerebrosidase activity and substrate accumulation of glycosphingolipids in a novel GBA1 D409V knock-in mouse model.PloS one · 2021Article
- Glial cells in Parkinson´s disease: protective or deleterious?Cellular and molecular life sciences : CMLS · 2020Review
- Plant Glycosides and Glycosidases: A Treasure-Trove for Therapeutics.Frontiers in plant science · 2020Review
- Neuronal Soma-Derived Degradative Lysosomes Are Continuously Delivered to Distal Axons to Maintain Local Degradation Capacity.Cell reports · 2019Article
- Are we listening to everything the PARK genes are telling us?The Journal of comparative neurology · 2019Review
- Localization of active endogenous and exogenous β-glucocerebrosidase by correlative light-electron microscopy in human fibroblasts.Traffic (Copenhagen, Denmark) · 2019Article
- Species-specific differences in nonlysosomal glucosylceramidase GBA2 function underlie locomotor dysfunction arising from loss-of-function mutations.The Journal of biological chemistry · 2019Article
- Functionalized Cyclophellitols Are Selective Glucocerebrosidase Inhibitors and Induce a Bona Fide Neuropathic Gaucher Model in Zebrafish.Journal of the American Chemical Society · 2019Article
- In vivo inactivation of glycosidases by conduritol B epoxide and cyclophellitol as revealed by activity-based protein profiling.The FEBS journal · 2019Article
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Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gaucher disease is characterized by lysosomal accumulation of glucosylceramide due to deficient activity of lysosomal glucocerebrosidase (GBA). In cells, glucosylceramide is also degraded outside lysosomes by the enzyme glucosylceramidase 2 (GBA2) of which inherited deficiency is associated with ataxias. The interest in GBA and glucosylceramide metabolism in the brain has grown following the notion that mutations in the GBA gene impose a risk factor for motor disorders such as α-synucleinopathies. We earlier developed a β-glucopyranosyl-configured cyclophellitol-epoxide type activity based probe (ABP) allowing in vivo and in vitro visualization of active molecules of GBA with high spatial resolution. Labeling occurs through covalent linkage of the ABP to the catalytic nucleophile residue in the enzyme pocket. Here, we describe a method to visualize active GBA molecules in rat brain slices using in vivo labeling. Brain areas related to motor control, like the basal ganglia and motor related structures in the brainstem, show a high content of active GBA. We also developed a β-glucopyranosyl cyclophellitol-aziridine ABP allowing in situ labeling of GBA2. Labeled GBA2 in brain areas can be identified and quantified upon gel electrophoresis. The distribution of active GBA2 markedly differs from that of GBA, being highest in the cerebellar cortex. The histological findings with ABP labeling were confirmed by biochemical analysis of isolated brain areas. In conclusion, ABPs offer sensitive tools to visualize active GBA and to study the distribution of GBA2 in the brain and thus may find application to establish the role of these enzymes in neurodegenerative disease conditions such as α-synucleinopathies and cerebellar ataxia.
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